Genetic Engineering Mice Models of Depressive-like or Depression-resistant Phenotype

doi:10.3969/j.issn.1674-5817.2015.02.012

Abstract

Abstract: The development of knockout or knockdown mice, showing a depressive or depression-resistant phenotype, have allowed us to better understand the complex relationship between genes, behavior and acquired disposition in mood disorders. Preclinical and clinical studies have established that a dysfunction of serotonin (5-HT) neurotransmission is a common hallmark in depression. Genetic mice models with a gene manipulation of?transporter, receptor, protein, enzyme gene in 5-HT system show depressive or depression-resistant phenotype. The present review revises ten genetically engineered mice models with mood alteration (either includes 5 genotypes) and summarizes their each physiological fuction,molecular mechanism, behavioristics,neurophysiology and even those translated to human. In turn, findings from human studies have helped to design and generate genetic mice models to explore new hypothesis of the etiology of human depression, and most important, to explore and refine new strategies for antidepressant medication.

Key words: Depression, Depression-resistance, Behavioral phenotype, Serotonin, Genetic Engineering, Mice models

CLC Number:

Q95-33

WANG Xiao-jie, ZHANG Zhi-jun, YE Dong-qing. Genetic Engineering Mice Models of Depressive-like or Depression-resistant Phenotype[J]. Laboratory Animal and Comparative Medicine, 2015, 35(2): 142-148.

References

[1] Rudnick G, Clark J.From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters[J]. Neuroscience, 2006, 140(1):321-334.
[2] Zhao S, Edwards J, Carroll J, et al.Insertion mutation at the C-terminus of the serotonin transporter disrupts brain serotonin function and emotion-related behaviors in mice[J]. Neuroscience, 2006, 140(1):321-334.
[3] Fabre V, Beaufour C, Evrard A, et al.Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter[J]. Eur J Neurosci, 2000, 12(7):2299-2310.
[4] Li Q, Wichems CH, Ma L, et al.Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice[J]. J Neurochem, 2003,84(6): 1256-1265.
[5] Murphy DL, Fox MA, Timpano KR, et al.How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems[J]. Neuropharmacology, 2008, 55(6):932-960.
[6] Compan V, Zhou M, Grailhe R, et al.Attenuated response to stress and novelty and hypersensitivity to seizures in 5-HT4 receptor knock-out mice[J]. J Neurosci, 2004, 24(2):412-419.
[7] Bockaert J, Claeysen S, Compan V, et al.5-HT4 receptors, a place in the sun: act two[J]. Curr Opin Pharmacol, 2011, 11(1):87-93.
[8] Conductier G., Dusticier N Lucas G., et al.Adaptive changes in serotonin neurons of the raphe nuclei in 5-HT4 receptor knock-out mouse[J]. Eur J Neurosci, 2006, 24(4):1053-1062.
[9] Doyle JM, Gao J, Wang J, et al.MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases[J]. Mol Cell, 2010, 39(6):963-974.
[10] Mouri A, Sasaki A, Watanabe K, et al.MAGE-D1 regulates expression of depression-like behavior through serotonin transporter ubiquitylation[J]. J Neurosci, 2012, 32(13):4562-4580.
[11] Warner-Schmidt JL, Schmidt EF, Marshall JJ, et al.Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior[J]. Proc Natl Acad Sci USA, 2012,109(28): 11360-11365.
[12] Egeland M, Warner-Schmidt J, Greengard P, et al.Co-expression of serotonin 5-HT1B and 5-HT4 receptors in p11 containing cells in cerebral cortex, hippocampus, caudate-putamen and cerebellum[J]. Neuropharmacology, 2011, 61(3): 442-450.
[13] Anisman H, Du L, Palkovits M, et al.Serotonin receptor subtype and p11 mRNA expression in stress-relevant brain regions of suicide and control subjects[J]. J Psychiatr Neurosci, 2008, 33(2):131-141.
[14] Svenningsson P, Kim Y, Warner-Schmidt J, et al.p11 and its role in depression and therapeutic responses to antidepressants[J]. Nat Rev Neurosci, 2013,14(10):673-680.
[15] Warner-Schmidt JL, Flajolet M, Maller A, et al.Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation[J]. J Neurosci, 2009, 29(6):1937-1946.
[16] Warner-Schmidt JL, Chen EY, Zhang X, et al.A role for p11 in the antidepressant action of brain-derived neurotrophic factor[J]. Biol Psychiat, 2010, 68(6):528-35.
[17] Diez H, JJ Garrido,F Wandosell. Specific roles of Akt iso forms in apoptosis and axon growth regulation in neurons[J]. PLoS One, 2012, 7(4):e32715.
[18] Leibrock C, Ackermann TF, Hierlmeier M, et al.Akt2 deficiency is associated with anxiety and depressive behavior in mice[J]. Cell Physiol Biochem, 2013, 32(3):766-777.
[19] Pineyro G and Blier P. Autoregulation of serotonin neurons:role in antidepressant drug action[J]. Pharmacol Rev, 1999, 51(3):533-591.
[20] Gunther L, Rothe J, Rex A, et al.5-HT1A-receptor over-expressing mice: genotype and sex dependent responses to antidepressants in the forced swim-test[J]. Neurop-harmacology, 2011, 61(3):433-441.
[21] Richardson-Jones JW, Craige CP, Guiard BP, et al.5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants[J]. Neuron, 2010, 65(1):40-52.
[22] Lemonde S, Turecki G., Bakish D, et al.Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide[J]. J Neurosci, 2003, 23(25):8788-8799.
[23] Parsey RV, Olvet DM, Oquendo MA, et al.Higher 5-HT1A receptor binding potential during a major depressive episode predicts poor treatment response: preliminary data from a naturalistic study[J]. Neuropsychopharmacol, 2006, 31(8): 1745-1749.
[24] Alloui A, Olvet DM,?Oquendo MA, et al. TREK-1, a K+ channel involved in polymodal pain perception[J]. Embo J, 2006, 25(11):2368-2376.
[25] Heurteaux C, Lucas G, Guy N, et al.Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype[J]. Nat Neurosci, 2006, 9(9):1134-1141.
[26] Liou YJ, Lucas G., Guy N, et al.Support for the involvement of the KCNK2 gene in major depressive disorder and response to antidepressant treatment[J]. Pharmacogenet and Genom, 2009, 19(10):735-741.
[27] Datar P, Srivastava S, Coutinho E, et al.Substance P: Structure, function, and therapeutics[J]. Curr Top Med Chem, 2004, 4(1):75-103.
[28] Froger N, Gardier AM, Moratalla R, et al.5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization[J]. J Neurosci, 2001, 21(20):8188-8197.
[29] Santarelli L, Gobbi G, Debs P, et al.Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function[J]. Proc Natl Acad Sci USA, 2001, 98(4):1912-1917.
[30] Frisch P, Srivastava S, Coutinho E, et al.Modulation of the CRH system by substance P/NKA in an animal model of depression[J]. Behv Brain Res, 2010, 213(1):103-108.
[31] Burnet PWJ and PJ Harrison. Substance P (NK1) receptors in the cingulate carter in unipolar and bipolar mood disorder and schizophrenia[J]. Biol Psychiat, 2000, 47(1):80-83.
[32] Stockmeier CA, Shi X, Konick L, et al.Neurokinin-I receptors are decreased in major depressive disorder[J]. Neuroreport, 2002, 13(9):1223-1227.
[33] Freund TF, Katona I and Piomelli D. Role of endogenous cannabinoids in synaptic signaling[J]. Physiol Rev, 2003, 83(3):1017-1066.
[34] Cassano T, Gaetani S, Macheda T, et al.Evaluation of the emotional phenotype and serotonergic neurotransmission of fatty acid amide hydrolase-deficient mice[J]. Psychoph-armacology, 2011, 214(2):465-476.
[35] Bambico FR, Cassano T, Dominguez-Lopez S, et al.Genetic deletion of fatty acid amide hydrolase alters emotional behavior and serotonergic transmission in the dorsal raphe, prefrontal cortex, and hippocampus[J]. Neuropsychophar-macol, 2010, 35(10):2083-2100.
[36] Siuciak JA.The role of phosphodiesterases in schizophrenia: therapeutic implications[J]. CNS Drugs, 2008,22(12):983-993.
[37] Schaefer TL, Braun AA, Amos-Kroohs RM, et al.A new model of Pde4d deficiency: genetic knock-down of PDE4D enzyme in rats produces an antidepressant phenotype without spatial cognitive effects[J]. Genes Brain Behav, 2012, 11(5):614-622.
[38] Levinson DF.The genetics of depression: a review[J]. Biol Psychiat, 2006, 60( 2):84-92.